ABSTRACT
INTRODUCTION: A recent randomized trial demonstrated that sorafenib improved progression free survival (PFS) in patients with desmoid tumors despite many patients experiencing stable disease or spontaneous regression without treatment. Utilizing these trial data, we performed a cost analysis of sorafenib efficacy through two years of treatment. METHODS: Current Medicare Part D rates for sorafenib were utilized (dose 400â mg/day, cost $309/day). Annual costs per progression and objective response were calculated. Radiologic progression and response were defined using RECIST criteria. Patients with disease progression were separately analyzed in two groups: both clinical and radiologic (CAR), and radiologic alone. RESULTS: 84 previously randomized patients were analyzed (placebo: 35, sorafenib: 49). At one year, sorafenib was associated with a 43% absolute risk reduction (ARR) of CAR progression and number-needed-to-treat (NNT) of 2.3 patients/year, costing $259,406. At two years, ARR was 48% and NNT of 2.1 patients/year, costing $473,697. When evaluating only patients with RECIST defined radiologic progression, sorafenib patients experienced ARR of 13.9% with NNT 7.2 and estimated costs of $812,052 at one year. Two-year ARR was 17.5% with NNT 5.7 and estimated costs $1,285,052. Sorafenib patients experienced improved RECIST partial response rates at 1 and 2 years of 14.7% and 14.3%, with NNT 6.8 and 6.9, and costs of $766,938 and $1,556,433; respectively. CONCLUSION: For the treatment of desmoid tumors, Sorafenib led to improved PFS, but at a significant cost per patient. Favorable RECIST outcomes were less likely and costlier. Patients should be informed of possible benefits of treatment versus potential financial burden.
Subject(s)
Fibromatosis, Aggressive , Aged , United States , Humans , Sorafenib/therapeutic use , Fibromatosis, Aggressive/drug therapy , Phenylurea Compounds/therapeutic use , Medicare , Costs and Cost Analysis , Treatment Outcome , Niacinamide/therapeutic useABSTRACT
BACKGROUND: Converging evidence suggests that cerebral metabolic and cellular homeostasis is altered in patients with recent onset of schizophrenia. As a possible marker of metabolic changes that might link to altered neurotransmission, we used proton magnetic resonance spectroscopy to estimate brain temperature, and we evaluated its relationship to a relevant metabolite, glutamate, within this study population. METHODS: Using proton magnetic resonance spectroscopy at 7T, 20 patients with recent onset (≤24 months after first psychotic symptoms) of schizophrenia and 20 healthy control subjects were studied. We measured levels of N-acetylaspartate and glutamate and estimated brain temperature in a noninvasive manner. RESULTS: Healthy control subjects showed a significant negative correlation between glutamate and brain temperature in the anterior cingulate cortex. In contrast, the physiological correlation between glutamate and brain temperature was lost in patients with recent onset of schizophrenia. CONCLUSIONS: This study supports the hypothesized disrupted relationship between brain metabolism and neurotransmission in patients with recent onset of schizophrenia. The findings include mechanistic implications that are to be followed up in both preclinical and clinical studies.